This proposal represents a request for a competitive renewal to extend our study of diagnostic heterogeneity among cocaine abusers. The major goal of the study was to identify possible subgroups of cocaine abusers based on rates and patterns of clinical features and associated psychopathology. A strong association was found between cocaine abuse and alcoholism, with over 60% of the cocaine abusers having problems with alcohol. Moreover, family history data revealed a remarkable elevation in risk of drug abuse among siblings of cocaine abusers. Direct interviews would be expected to yield even higher rates of drug abuse among the relatives. When taken together with findings from a parallel family study of alcoholism which also reveal a strong association between alcoholism and cocaine abuse, these data suggest that offspring of substance dependent parents have an extremely high risk of developing dependence themselves. Elevation in rates of substance abuse of this magnitude underscore the necessity to identify premorbid risk factors towards which prevention efforts should be directed. Therefore, we propose to continue and expand our study by: evaluating subtypes of cocaine abuse based on clinical features and comorbid diagnoses; conducting direct interviews with relatives and spouses to examine the co-aggregation of substance abuse and psychiatric disorders; obtaining a comparable sample of community controls with equivalent sociodemographic features and risk of exposure to drugs to enable discrimination of specific factors which lead to abuse and dependence, examining common factors in the transmission of alcoholism and cocaine abuse through comparison of cocaine abusers with samples of probands with opioid abuse, alcoholism, affective disorders and anxiety disorders and through comparison of the relatives of these probands; and identifying premorbid risk and protective factors for substance abuse through comprehensive assessment of the offspring. the design includes direct interviews of 250 probands and 250 high risk children, and direct interviews of 1450 spouses and first degree relatives of probands. The alarming epidemic of AIDS in the U.S. as a complication of intravenous drug use demonstrates the critical importance of the prevention of drug abuse and its consequences. The results of the present study could have major impact in elucidating the appropriate targets of preventive intervention for substance abuse.